Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves

Abstract

The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valve lesions. Serum samples were collected from 82 patients with severe AS and from 12 control subjects. Aortic valves were obtained from a subpopulation of 21 AS patients undergoing valve surgery and from 10 controls. Serum and valvular total cholesterol and noncholesterol sterols were measured by gas-liquid chromatography. Noncholesterol sterols, including both cholesterol precursors and sterols reflecting cholesterol absorption, were detected in serum samples and aortic valves. The higher the ratios to cholesterol of the cholesterol precursors and absorption markers in serum, the higher their ratios in the stenotic aortic valves (r 5 0.74, P , 0.001 for lathosterol and r 5 0.88, P , 0.001 for campesterol). The valvular ratio to cholesterol of lathosterol correlated negatively with the aortic valve area (r 5 20.47, P 5 0.045), suggesting attenuation of cholesterol synthesis with increasing severity of AS. The higher the absorption of cholesterol, the higher the plant sterol contents in stenotic aortic valves. These findings suggest that local accumulation of plant sterols and cholesterol precursors may participate in the pathobiology of aortic valve disease.

Do clinical and experimental investigations support an antiatherogenic role for dietary phytosterols/stanols?

“…In conclusion, these genetic variations in the ABCG8 gene may explain the premature atherosclerosis that is observed in affected patients (44). Increases in concentration of b-sitosterol and OF campesterol in the plasma and aortic valve tissue were observed in CVD patients (45) and in patients who have undergone carotid endarterectomy. Although the relevance of this finding is not fully understood (46), it supports a relationship between the plasma concentrations of PS and CVD.…”

Regulation of Intestinal Cholesterol Absorption: A Disease Perspective

“…Although ezetimibe and plant sterols reduced plasma cholesterol to a similar extent, however, a greater protective effect was shown by ezetimibe on atherosclerotic lesion area [105]. Some studies have raised concerns over the use of plant sterols that accumulate in vascular lesions with increasing supplementation [106]. Therefore, use of plant sterols as a therapeutic intervention needs further evaluation.…”

Preliminary Observations From Preliminary Trial Results

“…7 However, SEAS tested a novel hypothesis with regard to the effects of other sterols on the progression of aortic stenosis. Because plant sterols have been recovered from stenotic aortic valves, 8 SEAS investigators hypothesized that inhibition of sterol absorption by ezetimibe would produce more favorable effects for this compound compared with prior statin trials. Despite the pathological similarities between aortic valve stenosis and atherosclerosis, it is now clear that neither therapy for lowering low-density lipoproteins nor inhibition of phytosterol absorption can reduce the progression of aortic stenosis.…”